arXiv:2607.16934stat.APcs.AI2026-07

用电子病历数据挖掘药物对心衰患者的不同效果,发现潜在受益和受损人群。

Optimizing Clinical Trial Protocols Using EHR-Derived Heterogeneous Treatment Effects

  • 基于电子病历模拟临床试验,用元学习法估算个体化治疗效应
  • 识别出用药显著获益(死亡风险降80%)和显著有害(死亡风险升6.7倍)的亚组
  • 适合关注精准医疗、临床试验设计优化的研究者阅读

传统随机对照试验常因关注平均疗效而掩盖治疗反应的临床异质性。利用真实世界数据模拟临床试验并估计异质性治疗效应(HTE),为更精确高效的试验设计提供了新路径。本研究基于梅奥诊所云平台(MCC)电子健康记录,模拟了DAPA-HF试验,探究以HTE为导向的分层能否识别射血分数降低型心衰患者中达格列净与安慰剂差异化的治疗反应。全人群以全因死亡率为终点,采用Cox比例风险模型分析,HTE通过Meta-S学习器估计,亚组划分采用基于决策树的阈值法。在整体模拟队列中未观察到显著治疗差异(HR=1.681;95%CI:0.828–3.413;p=0.1507)。然而,与总体队列相比,基于HTE的分层识别出具有显著且方向相反治疗效应的亚组:低HTE亚组显示显著生存获益(HR=0.203;95%CI:0.087–0.476;p=0.0002),高HTE亚组则显示显著有害关联,死亡风险显著升高(HR=6.680;95%CI:2.759–16.171;p<0.0001)。结果表明,基于HTE的分层可揭示被总体分析掩盖的临床意义明确的有益与有害效应模式。

原文摘要 · Abstract (English)

Traditional randomized trials often obscure clinically meaningful heterogeneity in treatment response by focusing on average effects. Leveraging real-world data to emulate clinical trials and estimate heterogeneous treatment effects (HTEs) offers a promising path toward more precise and efficient trial design. In this study, we emulate the DAPA-HF trial using electronic health records from the Mayo Clinic Cloud (MCC) to investigate whether HTE-guided stratification can identify patient subgroups with distinct treatment responses to dapagliflozin versus placebo in patients with heart failure with reduced ejection fraction. All-cause mortality was evaluated using Cox proportional hazards models, with HTEs estimated using a Meta-S learner and subgroups defined using a decision tree-based thresholding approach. In the overall cohort of the emulation, no significant treatment difference was observed (HR, 1.681; 95% CI, 0.828-3.413; p = 0.1507). However, compared with the overall emulated cohort, in which dapagliflozin showed no statistically significant survival benefit, HTE-driven stratification identified subgroups with significant and directionally distinct treatment effects. The beneficial (low-HTE) subgroup showed a significant survival benefit from dapagliflozin (HR = 0.203, 95% CI, 0.087-0.476, p = 0.0002), whereas the harmful (high-HTE) subgroup showed a significant harmful association with markedly increased mortality risk (HR = 6.680, 95% CI, 2.759-16.171, p < 0.0001). These findings indicate that HTE-guided stratification can uncover clinically meaningful beneficial and harmful treatment-effect patterns that are masked in the full-cohort emulation.

精准医疗真实世界数据治疗异质性电子病历

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